The goal of this project is to explore immunological mechanisms of disease and immunopathological processes. A failure of immune regulation is suspected to be involved in the super-normal production of auto antibodies in systemic lupus erythematosus (SLE). Treatment of normal T cells with serum from patients with SLE leads to increased proliferative and cytotoxic responses, indicating that such treatment has removed a naturally occurring suppressor cell. Absence of such suppressor cells in patients with SLE may lead to increased auto antibody formation. Immunologically mediated inflammation is often accompanied by the late onset of fibrosis. We have shown that supernatants from mixed lymphocyte reactions contain IL-1 or a closely related factor which is capable of inducing fibroblast proliferation. The local production of IL-1 by monocytes in areas of immunologically mediated inflammation may therefore be the reason for the fibrosis observed. Another pathological process that we are investigating is the mechanism through which P. falciparum infected erythrocytes attach to umbilical vein endothelial cells. Antibodies in the sera of infected monkeys block this interaction and may provide a means to explore the nature of the receptors on the infected RBC and the endothelial cells involved in this process.